Designing vitamin D3 formulations: novel micellar delivery system tested

Functioning as a steroidal hormone, vitamin D is synthesised by skin cells upon sunlight irradiation. It may also be obtained, to a lesser extent, from dietary sources, but Vitamin D deficiency (VDD) is a prolific health issue, especially in countries with less sunlight and more indoor lifestyles.

As a result, oral Vitamin D supplements are regularly recommended. Most often, Vitamin D is supplied in the form of Vitamin D3, otherwise known as cholecalciferol.

Ideally, orally supplemented Vitamin D3 should be completely absorbed through the intestinal mucosa. However, immiscibility between this hydrophobic compound and the aqueous gut environment, combined with interference caused by other compounds such as cholesterol, can severely hinder the absorption process.

Efforts have therefore aimed at refining delivery technology for optimal absorption of the supplemented vitamin.

Typically, the refined delivery vehicles have involved the creation of minute particle sizes which are expected to have a finer dispersion of the target compound and a greater surface area for enhanced absorption.

While liposomal formulations hold promise for improved solubility and absorption​, micellar formulations​ have also been explored, with a focus on reducing the particle size of the delivery vehicles and creating nanoparticles and nanostructured lipid carriers.

LipoMicel technology is one such example, developed to improve the solubility and stability of various compounds by encapsulating the active compound in a lipid-based matrix and creating a natural emulsion.

In addition to particle size, there is increasing evidence that cell–matrix adhesion and specific receptor carriers may also play key roles in influencing absorption by using micellar delivery systems​.

Thus, the current study, conducted in Canada, aimed to evaluate three novel vitamin D3 formulations based on the LipoMicel technology using Caco-2 as an in vitro cell model compared to a control/basic formula (Vitamin D3 and carrier oil).

The resulting data indicate that one LipoMicel formulation, despite having a similar particle-size range and solubilities as the control, showed significantly improved permeability (12,000 times more permeable compared to the baseline control), suggesting that more complex biological mechanisms may be involved. 

The study concludes: "Overall, LipoMicel has the potential to be effective at improving the oral absorption of Vitamin D3 and stands to benefit from further in vivo experiments to determine bioavailability in humans."

Study details

Three different novel formulations (LM1, LM2 and LM3, where LM was abbreviated from “LipoMicel”) were assessed for their solubility and permeability against the control. All formulas were provided by the Factors Group of Nutritional Companies. 

Morphological and physicochemical properties of the most promising formula were also assessed.

Common excipients were shared between LM1, LM2 and LM3 as follows: medium chain triglycerides, Xylitol, Methylsulfonylmethane. Excipients unique to each formula were the followin: glycerin, saponin and ethanol were present in LM1; stevia and lecithin were present in LM2; cocoa was present in LM3. The combinations of these are proprietary.

Significantly, Caco-2 permeability experiments showed that LipoMicel is 12,000 times more permeable compared to the baseline control. This is several orders of magnitude higher than the 2.5 times enhanced uptake reported on lysophosphatidylcholine micelles​, the 4-fold increase in bioavailability reported in a casein micelles​ and the 5.3-fold increase reported in pea-protein-based nanoemulsions​.

However, in this study it appears that the increased permeability of micellar Vitamin D3 does not correlate with increased solubility or reduced particle size—since LipoMicel has similar solubility characteristics and particle size distribution as the baseline control.

While other reports on Vitamin D micelles​ focused on structural morphology, stability, bioaccessibility and controlled release without reporting permeability, this study demonstrates that biological experiments provide better insights on Vitamin D absorption than simple diffusion modelled by physical and chemical characterization of the formulations​.

The authors explain: "The results of our study suggest that the absorption process involves biological mechanisms such as cholesterol transporters and cell-membrane efflux pumps such as ABCB1, which would support previous findings​. However, this assumption needs to be further evaluated in future studies."

Source: Nutraceuticals

https://doi.org/10.3390/nutraceuticals3020023​

"Designing Vitamin D3 Formulations: An In Vitro Investigation Using a Novel Micellar Delivery System"

Du, M.; Chang, C.; Zhang, X.; Zhang, Y.; Radford, M.J.; Gahler, R.J.; Kuo, Y.C.; Wood, S.; Solnier, J.